Remission Of Depressive Symptoms Research Articles

Interactive Q-Learning for Quantiles

ABSTRACT A dynamic treatment regime is a sequence of decision rules, each of which recommends treatment based on features of patient medical history such as past treatments and outcomes. Existing methods for estimating optimal dynamic treatment regimes from data optimize the mean of a response variable. However, the mean may not always be the most appropriate summary of performance. We derive estimators of decision rules for optimizing probabilities and quantiles computed with respect to the response distribution for two-stage, binary treatment settings. This enables estimation of dynamic treatment regimes that optimize the cumulative distribution function of the response at a prespecified point or a prespecified quantile of the response distribution such as the median. The proposed methods perform favorably in simulation experiments. We illustrate our approach with data from a sequentially randomized trial where the primary outcome is remission of depression symptoms. Supplementary materials for this article are available online.

T20 - New Insights Into The Pharmacogenomics Of Antidepressant Response From The Gendep And Star*D Studies: Results Of Rare Variant Analysis And High-Density Imputation

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons are limited coverage of genetic variants, phenotypic heterogeneity and small sample size. This study investigated the genetic predictors of antidepressant efficacy in Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) samples trying to address some of the reported limitations. In detail: 1) coverage of genetic variants was increased by adding exome array data to previously available genome-wide data and by genotype imputation using the largest available reference panel (Haplotype Reference Consortium (HRC)); 2) a meta-analysis was performed using SNP methods and multi-marker tests at gene and pathway level. Each dataset was imputed using Minimac3 and the HRC panel after standard quality control. Both samples included patients with diagnosis of major depressive disorder. In GENDEP, patients were partially randomized to escitalopram or nortriptyline; STAR*D patients were treated with citalopram. Escitalopram is the active isomer of citalopram, thus the whole GENDEP sample and the escitalopram-treated subgroup were meta-analyzed with STAR*D. The phenotypes were depressive symptom improvement and remission at week 12 according to standard scales. SNP-level analysis was performed using PLINK (pngu.mgh.harvard.edu/~purcell/plink/); gene and pathway analyses were performed using MAGMA (http://ctglab.nl/software/magma). Covariates were age, baseline severity, center of recruitment and ancestry-informative principal components. NEWMEDS (http://www.newmeds-europe.com) consortium samples, excluding GENDEP, served for replication. 7,062,950 SNPs were analysed in GENDEP (n=738) and STAR*D (n=1409). There was no evidence of genomic inflation (lambda values were ≤ 1.01). No SNP was associated with symptom improvement or remission in the full meta-analysis. In the citalopram/escitalopram analysis, rs116692768 (MAF=0.033, p=1.87e-08, ITGA9 or integrin alpha 9 gene) and rs76191705 (MAF=0.012, p=2.39e-08, NRXN3 or neurexin 3 gene) were associated with symptom improvement. At gene level (whole sample), OR4K2 was associated with improvement (corrected p=0.04), but its effect was inconsistent between the samples. At pathway level (whole sample), the Gene Ontology terms GO:0005694 (chromosome) and GO:0044427 (chromosomal part) were associated with improvement (corrected p=0.007 and 0.045, respectively). Genome-wide significant SNPs were not replicated in NEWMEDS SSRI-treated sample (n=751) (p>0.05). ITGA9 and NRXN3 show a meaningful biological rationale for being involved in antidepressant effect. ITGA9 codes for a membrane glycoprotein receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in post-synaptic and pre-synaptic differentiation, with relevant implications for synaptic activity and synaptic plasticity. Interestingly, rs76191705 is a non-sense mediated decay transcript variant and a polymorphism in complete LD with it (rs79302561) acts as an enhancer of gene expression (Ensembl GRCh37 release 84). However, no convincing replication of these findings was achieved and further studies may be useful to clarify the role of these genes in antidepressant efficacy.

Sleep at baseline and after electroconvulsive therapy in patients with major depression.

Sleep in major depressive disorder is frequently altered and possibly indicative for treatment outcomes. For example, increased rapid eye movement (REM-) sleep density seems to predict worse treatment outcomes of psychotherapy. We therefore investigated pre-treatment sleep and sleep changes after termination of electroconvulsive therapy (ECT). Sleep was polysomnographically recorded. The analysed sample consisted of 15 inpatients with ages ranging from 30 to 80 (mean 59 years). ECT was applied two times a week up to 7 weeks. Stable remission of depressive symptoms was defined by a score in the Hamilton Rating Scale of Depression <8 at six months after ECT. The main results were an increase in sleep efficiency and a decrease in the number of awakenings within the course of ECT in the entire patient group. Significant increases in slow wave sleep and REM sleep duration and a significant decrease in REM density were only seen in stable remitters and not in non-remitters. In pre-treatment baseline sleep a higher REM density of the first REM sleep period was significantly associated with better ECT outcome. In conclusion, REM density of the first REM sleep period seems to be an interesting candidate as putative predictor of stable treatment outcome of ECT.

Longitudinal Changes in Depression Symptoms and Survival Among Patients With Lung Cancer: A National Cohort Assessment.

Purpose Depression symptoms are common among patients with lung cancer; however, longitudinal changes and their impact on survival are understudied. Methods This was a prospective, observational study from the Cancer Care Outcomes Research and Surveillance Consortium from five US geographically defined regions from September 2003 through December 2005. Patients enrolled within 3 months of their lung cancer diagnosis were eligible. The eight-item Center for Epidemiologic Studies Depression scale was administered at diagnosis and 12 months' follow-up. The main outcome was survival, which was evaluated using Kaplan-Meyer curves and adjusted Cox proportional hazards modeling. Results Among 1,790 participants, 681 (38%) had depression symptoms at baseline and an additional 105 (14%) developed new-onset depression symptoms during treatment. At baseline, depression symptoms were associated with increased mortality (hazard ratio [HR], 1.17; 95% CI, 1.03 to 1.32; P = .01). Participants were classified into the following four groups based on longitudinal changes in depression symptoms from baseline to follow-up: never depression symptoms (n = 640), new-onset depression symptoms (n = 105), depression symptom remission (n = 156), and persistent depression symptoms (n = 254) and HRs were calculated. Using the never-depression symptoms group as a reference group, HRs were as follows: new-onset depression symptoms, 1.50 (95% CI, 1.12 to 2.01; P = .006); depression symptom remission, 1.02 (95% CI, 0.79 to 1.31; P = .89), and persistent depression symptoms, 1.42 (95% CI, 1.15 to 1.75; P = .001). At baseline, depression symptoms were associated with increased mortality among participants with early-stage disease (stages I and II; HR, 1.61; 95% CI, 1.26 to 2.04), but not late-stage disease (stages III and IV; HR, 1.05; 95% CI, 0.91 to 1.22). At follow-up, depression symptoms were associated with increased mortality among participants with early-stage disease (HR, 1.71; 95% CI, 1.27 to 2.31) and those with late-stage disease (HR, 1.32; 95% CI, 1.04 to 1.69). Conclusion Among patients with lung cancer, longitudinal changes in depression symptoms are associated with differences in mortality, particularly among patients with early-stage disease. Symptom remission is associated with a similar mortality rate as never having had depression.

Escitalopram but not placebo modulates brain rhythmic oscillatory activity in the first week of treatment of Major Depressive Disorder

Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5–8 Hz) and the alpha (8–12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms. Prefrontal delta-theta and alpha power were calculated for 194 subjects with moderate MDD prior to and one week after start of treatment. Changes at one week in delta-theta and alpha power, as well as the delta-theta/alpha ratio, were examined in three cohorts: initial (N = 70) and replication (N = 76) cohorts treated with escitalopram, and a cohort treated with placebo (N = 48). Mean delta-theta power significantly increased and alpha power decreased after one week of escitalopram treatment, but did not significantly change with placebo treatment. The delta-theta/alpha ratio change was a specific predictor of the likelihood of remission after seven weeks of medication treatment: a large increase in this ratio was associated with non-remission in escitalopram-treated subjects, but not placebo-treated subjects. Escitalopram and placebo treatment have differential effects on delta-theta and alpha frequency oscillations. Early increase in delta-theta/alpha may constitute a replicable biomarker for non-remission during SSRI treatment of MDD.

Surrogate markers of visceral fat and response to anti-depressive treatment in patients with major depressive disorder: a prospective exploratory analysis

Background: Body mass index (BMI) and body weight have been shown to be associated to treatment outcome in patients with major depressive disorder, but this relationship is not clear. Visceral fat might be an underlying mechanism explaining this relationship.Aims: The aim of this study was to prospectively investigate whether visceral fat, as measured by hip-to-waist ratio and waist circumference, affects treatment outcome in patients with major depressive disorder in patients attending a hospital psychiatric care unit in Denmark.Methods: The study was conducted as an observational prospective study including 33 patients with major depressive disorder. Assessments were made at enrolment and after 8 weeks. Primary variables were hip-to-waist ratio and waist circumference. Outcome were remission or response of depressive symptoms measured with the Hamilton Depression Rating Scale (HAM-D17) interviews and HAM-D6 self-rating questionnaires.Results: No differences were found in outcome between groups of patients with high vs low visceral fat in this population.Conclusions: The lack of association was evident for all surrogate markers of visceral fat, and suggests that visceral fat has no impact on outcomes of depressive symptoms. However, study limitations might have contributed to this lack of association, especially sample size and considerable variations on multiple parameters including treatment received during the 8 weeks of follow-up.

Continuation phase intravenous ketamine in adults with treatment-resistant depression

BackgroundLittle is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. MethodsTwelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only). ResultsOf the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up. LimitationsThis was an uncontrolled feasibility study with a small sample size. ConclusionsThe continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. ClinicalTrials.gov identifierNCT02094898.

Funciones ejecutivas en la depresión

Executive functions (EF) have been defined as all the cognitive processes needed to formulate, plan and execute a goal. EF were initially studied in traumatic brain injuries or central nervous system lesions. Recent research has shown that cognitive alterations (and, in particular, EF) are a central manifestation of mental disorders, including depression. Patients with response and even remission of depressive symptoms still have residual symptoms related to EF. The differences found in EF alterations are influenced by the severity of the depression, the clinical subtype, age, comorbidities and the distinct treatments. Both pharmacological and non-pharmacological treatments of depression should give priority to these clinical and research findings.

Cognición en remisión

Cognitive impairments are common in the context of major depressive disorder. Nowadays, there is growing evidence confirming that these alterations are present not only during acute or active depressive episodes, but that they persist for some time after significant remission of depressive symptoms in a substantial percentage of patients who have suffered from this disorder.This study reviews the literature that has addressed this issue with a view to defining the profile and pattern of cognitive dysfunction in remitted depression and establishing its clinical and functional impact. Various studies have assessed impaired cognitive functioning after remission and have demonstrated alterations in distinct cognitive domains; the most important of these alterations involve dysfunctions in attention, memory and executive function.The presence of these alterations significantly affects the patient's functional performance and quality of life and increases the risk of further depressive relapses. There is a need for increased efforts to adequately assess the presence of these alterations in patients who have had depressive symptoms and to develop appropriate therapeutic strategies for their effective management.

Overcoming functional impairment in postpartum depressed or anxious women: a pilot trial of desvenlafaxine with flexible dosing.

Antidepressants are the first line treatment for moderate to severe major depressive disorder (MDD) in perinatal and general populations. However, there appears to be paucity of evidence around antidepressant use in women with postpartum depression or anxiety. Selection of an appropriate antidepressant is crucial in promoting efficacy, optimizing tolerability, and managing comorbid anxiety or depression. Our aim was to investigate the treatment effect and tolerability profile of desvenlafaxine, and to examine the functionality of women with postpartum depression or anxiety after desvenlafaxine treatment. Fifteen postpartum women with depression or anxiety completed this 12-week prospective pilot study with a flexible dose of desvenlafaxine (50-100 mg). Participants were recruited at a tertiary care level program. Measures of depression (Montgomery-Åsberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAM-A), worry (Penn State Worry Questionnaire, PSWQ) and functional impairment (Sheehan Disability Scale, SDS) were completed at baseline, 8 weeks, and 12 weeks. In the intention-to-treat analysis (n = 17), the majority of women responded to medication (88.2%, n = 15), and reached remission of depressive (82.4%, n = 14) and anxiety symptoms (82.4%, n = 14). Remission of depression was achieved in a mean of 6.9 weeks [standard deviation (SD) = 3.01] at a mean dose of 71 mg/day (SD = 25.7). Significant decreases were observed on PSWQ worry scores (p < 0.0001) and SDS scores for social (p < 0.0001) and family life impairment (p < 0.0001). The medication was generally well tolerated. The results of our prospective pilot study suggest that treatment with desvenlafaxine of postpartum mothers with depression or anxiety can lead to symptom remission and restoration of functionality.

Antidépresseurs et tolérance : déterminants et prise en charge des principaux effets indésirables

Antidepressant therapy aims to reach remission of depressive symptoms while reducing the complications and risks of relapse. Even though they have proven their efficacy, it takes several weeks for antidepressants to demonstrate full effectiveness, and adverse effects occur more quickly or (quicker) which can be a source of poor compliance. This latest aspect often leads to dose reduction and/or change of molecule that have the effect of delaying remission. This review attempts to present, from the pharmacological properties of the major classes of antidepressants (monoamine oxidase inhibitor [MAOI], tricyclic antidepressants [TCA], selective serotonin reuptake inhibitor [SSRI] and serotonin and noradrenaline reuptake inhibitor [SNRI]), to the pharmacological mechanisms involved in adverse effects by focusing on sexual dysfunction, nausea/vomiting, and weight changes and sleep disruption. If the activation of dopamine D1/2 or norepinephrine receptors through the autonomic nervous system controls and facilitates sexual desire, increasing serotoninergic transmission through 5-HT1B/2A/2C receptors activation inhibits this process. The pharmacological properties of drugs inducing nausea/vomiting activate opiate receptors μ, increase dopaminergic and serotoninergic transmission activating the dopamine D2 and serotonin 5-HT3 receptors, respectively. Among the causes responsible for weight gain under antidepressant therapy, monoamine neurotransmission still plays an important role. The blockade of serotonin 5-HT2C or histamine H1 receptors is directly responsible for weight gain. Finally, the activation of 5-HT1A/1B/3/7 serotoninergique receptors modulates wakefulness, raid eyes movement or sleep duration. In conclusion, if antidepressant activity of SERT or MAO inhibitors is an indirect consequence of postsynaptic 5-HT, DA, NA receptor activation, it is also responsible for side effects, causes of poor compliance and hence therapeutic failures. Finally, we need to take into account the key role of the nocebo effect in the occurrence of adverse effects. The next generation of antidepressant would aim to have a rapid efficacy in patients unresponsive or resistant to drugs currently available while improving certain effects of tolerance through an optimization of their psychopharmacological properties leading to a reduction of their side effects.

Screening for Depression—A Tale of Two Questions

The US Preventive Services Task Force (USPSTF)1 has issued new recommendations on Screening for Depression inwhich they concluded, “TheUSPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women. Screening should be implemented with adequate systems in place to ensure accuratediagnosis, effective treatment, andappropriate follow-up (B recommendation).”GradeB indicateshighcertainty that the netbenefit ismoderateormoderate certainty that thenetbenefit is moderate to substantial. An “adequate system” includes a depression care manager who ensures that patients are screened and, if they screen positive for depression, appropriatelydiagnosedandtreatedwithevidence-basedstepped careor referred toa setting that canprovide thenecessarycare. The newguidelines are similar to the 2002 and 2009USPSTF depression screening recommendations except for 1 major change:neither the2002nor the2009recommendationsmentioned pregnant or postpartumwomen.2,3 The recentUSPSTF recommendations are largelybasedon a systematic review evaluating the potential benefits of depressionscreening inpregnantorpostpartumwomen.4Nonew randomized trials of depression screening in (nonpregnant or postpartum) adults have been added since the 2009 guidelines. One example of the new studies included in the USPSTF systematic review was a trial that randomized 462 postpartum women (who were not already receiving psychiatric treatment) toadepressionscreening interventionvsusual care.5 Intervention groupparticipants completed the 10-item Edinburgh Postnatal Depression Scale (EPDS); control group participants completed a general self-efficacy scale (similar in length and format) but didnot complete theEPDS.All participants underwent a clinical assessment by a nurse who was blinded to their group allocation; patients (fromeither group) who were assessed by this nurse as having probable postnatal depression were referred for further evaluation and treatment. Intervention patients with an EDPS score of at least 10 (or any suicidal ideation)were referred for further evaluation and treatment (regardless of the clinical assessment). In an intention to treat analysis, 13% of the intervention group and 22.1% of the control group had EDPS scores of at least 10 at 6 months (risk ratio, 0.59; 95% CI, 0.39-0.89; number needed to screen, 11). Basedon this andother studies, theUSPSTFconcluded that screening results in the reduction or remission of depression symptoms and that the magnitude of harms of screening for depression in adults is small to none. Whether the available evidence justifies routine screening of unselected adults for depression is debatable. Notably, the Canadian Task Force on Preventive Health Care does not recommend routine screening for depression in adults at average risk.6 However, multiple other organizations (eg, American Academy of Family Physicians, American College of Physicians,AmericanCollegeofObstetriciansandGynecologists)do recommendroutinescreeningfordepression,especially forsubgroupsofpatientswhoareathighrisk, suchaspersonswith low socioeconomic status, limitedsocial support, chronicpain,disability, unintended pregnancy, comorbid mental health issues, or chronicmedical conditions.Moreover,most US insuranceproviders, including theCenter forMedicareandMedicaid Services, coverannual screening fordepression inprimarycare settingsthathavestaff-assisteddepressioncaresupports inplace to assure accurate diagnosis, effective treatment, and followup.Therefore,primarycarecliniciansmustbefamiliarwithhow to implement a depression screening program.

Mirtazapine added to selective serotonin reuptake inhibitors for treatment-resistant depression in primary care (MIR trial): study protocol for a randomised controlled trial.

BackgroundPeople with depression are usually managed in primary care and antidepressants are often the first-line treatment, but only one third of patients respond fully to a single antidepressant. This paper describes the protocol for a randomised controlled trial (MIR) to investigate the extent to which the addition of the antidepressant mirtazapine is effective in reducing the symptoms of depression compared with placebo in patients who are still depressed after they have been treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) for at least 6 weeks in primary care.Methods/DesignMIR is a two-parallel group, multi-centre, pragmatic, placebo controlled, randomised trial with allocation at the level of the individual. Eligible participants are those who: are aged 18 years or older; are currently taking an SSRI/SNRI antidepressant (for at least 6 weeks at an adequate dose); score ≥14 on the Beck Depression Inventory (BDI-II); have adhered to their medication; and meet ICD-10 criteria for depression (assessed using the Clinical Interview Schedule-Revised version).Participants who give written, informed consent, will be randomised to receive either oral mirtazapine or matched placebo, starting at 15 mg daily for 2 weeks and increasing to 30 mg daily thereafter, for up to 12 months (to be taken in addition to their usual antidepressant). Participants, their GPs, and the research team will all be blind to the allocation. The primary outcome will be depression symptoms at 12 weeks post randomisation, measured as a continuous variable using the BDI-II.Secondary outcomes (measured at 12, 24 and 52 weeks) include: response (reduction in depressive symptoms (BDI-II score) of at least 50 % compared to baseline); remission of depression symptoms (BDI-II <10); change in anxiety symptoms; adverse effects; quality of life; adherence to antidepressant medication; health and social care use, time off work and cost-effectiveness. All outcomes will be analysed on an intention-to-treat basis.A qualitative study will explore patients’ views and experiences of either taking two antidepressants, or an antidepressant and a placebo; and GPs’ views on prescribing a second antidepressant in this patient group.DiscussionThe MIR trial will provide evidence on the clinical and cost-effectiveness of mirtazapine as an adjunct to SSRI/SNRI antidepressants for patients in primary care who have not responded to monotherapy.Trial registrationEudraCT Number: 2012-000090-23 (Registered January 2012); ISRCTN06653773 (Registered September 2012)

The effectiveness and cost-effectiveness of the peer-delivered Thinking Healthy Programme for perinatal depression in Pakistan and India: the SHARE study protocol for randomised controlled trials.

BackgroundRates of perinatal depression (antenatal and postnatal depression) in South Asia are among the highest in the world. The delivery of effective psychological treatments for perinatal depression through existing health systems is a challenge due to a lack of human resources.This paper reports on a trial protocol that aims to evaluate the effectiveness and cost-effectiveness of the Thinking Healthy Programme delivered by peers (Thinking Healthy Programme Peer-delivered; THPP), for women with moderate to severe perinatal depression in rural and urban settings in Pakistan and India.Methods/DesignTHPP is evaluated with two randomised controlled trials: a cluster trial in Rawalpindi, Pakistan, and an individually randomised trial in Goa, India. Trial participants are pregnant women who are registered with the lady health workers in the study area in Pakistan and pregnant women attending outpatient antenatal clinics in India. They will be screened using the patient health questionnaire-9 (PHQ-9) for depression symptoms and will be eligible if their PHQ-9 is equal to or greater than 10 (PHQ-9 ≥ 10). The sample size will be 560 and 280 women in Pakistan and India, respectively. Women in the intervention arm (THPP) will be offered ten individual and four group sessions (Pakistan) or 6–14 individual sessions (India) delivered by a peer (defined as a mother from the same community who is trained and supervised in delivering the intervention). Women in the control arm (enhanced usual care) will receive health care as usual, enhanced by providing the gynaecologist or primary-health facilities with adapted WHO mhGAP guidelines for depression treatment, and providing the woman with her diagnosis and information on how to seek help for herself. The primary outcomes are remission and severity of depression symptoms at the 6-month postnatal follow-up. Secondary outcomes include remission and severity of depression symptoms at the 3-month postnatal follow-up, functional disability, perceived social support, breastfeeding rates, infant height and weight, and costs of health care at the 3- and 6-month postnatal follow-ups. The primary analysis will be intention-to-treat.DiscussionThe trials have the potential to strengthen the evidence on the effectiveness and cost-effectiveness of an evidence-based psychological treatment recommended by the World Health Organisation and delivered by peers for perinatal depression. The trials have the unique opportunity to overcome the shortage of human resources in global mental health and may advance our understanding about the use of peers who work in partnership with the existing health systems in low-resource settings.Trial registrationPakistan Trial: ClinicalTrials.gov Identifier: NCT02111915 (9 April 2014)India Trial: ClinicalTrials.gov Identifier: NCT02104232 (1 April 2014)

Study to Answer What Comes Next When MDD Patients Don’t Respond

VAST-D will provide valuable information about difficult-to-treat depression in a predominantly male population, including a relatively high proportion with comorbidities such as substance and alcohol use disorders and PTSD.

Challenging Treatment-Resistant Major Depressive Disorder: A Roadmap for Improved Therapeutics.

Major depressive disorder (MDD) is associated with a significant burden and costs to the society. As remission of depressive symptoms is achieved in only one-third of the MDD patients after the first antidepressant trial, unsuccessful treatments contribute largely to the observed suffering and social costs of MDD. The present article provides a summary of the therapeutic strategies that have been tested for treatment-resistant depression (TRD). A computerized search on MedLine/PubMed database from 1975 to September 2014 was performed, using the keywords “treatment-resistant depression”, “major depressive disorder”, “adjunctive”, “refractory” and “augmentation”. From the 581 articles retrieved, two authors selected 79 papers. A manual searching further considered relevant articles of the reference lists. The evidence found supports adding or switching to another antidepressant from a different class is an effective strategy in more severe MDD after failure to an initial antidepressant trial. Also, in subjects resistant to two or more classes of antidepressants, some augmentation strategies and antidepressant combinations should be considered, although the overall response and remission rates are relatively low, except for fast acting glutamatergic modulators. The wide range of available treatments for TRD reflects the complexity of MDD, which does not underlie diverse key features of the disorder. Larger and well-designed studies applying dimensional approaches to measure efficacy and effectiveness are warranted.

The Effect of a Brief Intervention for Patients with Ischemic Stroke: A Randomized Controlled Trial

Depression and anxiety are common after stroke. There is inconclusive evidence of the benefit of psychotherapy for poststroke depression and anxiety. Here, we used a brief intervention, Neuro-Linguistic Programming (NLP) brief therapy plus health education, to evaluate the changes in patients with ischemic stroke. One hundred eighty patients were randomly allocated to receive 4 sessions of NLP plus health education (n = 90) or usual care (n = 90). A set of questionnaires was used preintervention and postintervention as well as at the 6-month follow-up. The primary outcomes were the prevalence of depression and anxiety, and the awareness of stroke knowledge. More patients in the intervention group achieved remission of depressive (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.41-5.59) and anxious symptoms (OR, 2.19; 95% CI, 1.15-4.18) after intervention. At the 6-month follow-up, we found no differences between groups in both the prevalence of depression and anxiety. After intervention, the intervention group had better awareness rates on most of the stroke knowledge items (P < .05). It also had better quality of life and physical function both after intervention and at the follow-up (P < .05). NLP plus health education could reduce depression and anxiety immediately after intervention, but not at the 6-month follow-up. The intervention could also improve the awareness of stroke knowledge and benefit patients on quality of life and physical function.

Complex coevolution of depression and health-related quality of life in old age.

To investigate the coevolution of depression and health-related quality of life (HRQoL) in old age. In a representative survey of the German general population aged 75 years and older, the course of HRQoL and depression was observed over 4.5 years (3 waves). HRQoL was assessed by the Visual Analogue Scale (EQ VAS) of the EQ-5D instrument, while the Geriatric Depression Scale was used to measure depression. A panel vector autoregressive model was used to account for the complex coevolution of depression and HRQoL. Unobserved heterogeneity was taken into account by taking the first differences. We revealed a robust negative association between an initial change in HRQoL and a subsequent change in depression score, with substantial sex differences: In women there was a robust association, while in men the significance of this association depended on the model specification. Surprisingly, in the total sample and in both sexes, no robust association between an initial increase in depression and a subsequent change in HRQoL was found. Findings indicate that the direction of evolution from HRQoL to depression deserves more attention. Furthermore, treatment of depression in late life should aim at improving HRQoL in which remission of depressive symptoms is necessary but not sufficient.

Older Adults With Depression, Cognitive Impairment May Benefit From Psychosocial Therapy

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessOlder Adults With Depression, Cognitive Impairment May Benefit From Psychosocial TherapyVabren WattsVabren WattsSearch for more papers by this authorPublished Online:15 May 2015https://doi.org/10.1176/appi.pn.2015.5a15AbstractWith rates of cognitive impairment in older adults on the rise, experts are looking for new ways to help patients adapt and adjust emotionally.Because studies have shown antidepressant treatment to bring remission to less than 40 percent of elderly patients with depression—and even less among those who are also experiencing cognitive deficits—some researchers in geriatric mental health are beginning to adapt existing nonpharmacological approaches and explore new ones to alleviate specific psychiatric symptoms in older adults.At this year’s annual meeting of the American Association for Geriatric Psychiatry in New Orleans in March, researchers from the University of Pittsburgh School of Medicine (UPSOM) and Weill Cornell Medical College led a session on psychosocial interventions to help individuals mentally adapt to changes that often occur in late life.Mark Miller, M.D., says that more health care professionals should be trained to provide psychosocial services to the growing number of people with cognitive impairment and depression.Vabren Watts“New onset or recurrent depression is common in older patients experiencing retirement, relocation, disabilities, or loss of important people in their lives,” said Mark Miller, M.D., a professor of psychiatry at UPSOM, as he discussed interpersonal psychotherapy for cognitive impairment (IPTci).“Interpersonal psychotherapy to treat depression has been around for a while,” Miller told Psychiatric News, “but we have adapted it for use in patients with cognitive impairment as well as depression.” Some of the adaptations include assessing the mental health of the caregiver, shortening sessions to ease physical discomfort of patients, accommodating for hearing loss, arranging transportation, and conducting sessions by telephone when patients are ill or shut in by inclement weather. Though IPTci has yet to be extensively studied, Miller expressed optimism that clinicians are likely to find IPTci to be easy to use and well suited for addressing depression stemming from common late-life issues, such as medical illnesses, marital strains from taking care of an ill partner, and income reductions due to retirement. Caregivers of those with cognitive impairment are also included in IPTci treatment, which lasts 12 to 16 weeks. Miller and colleagues are recruiting participants for a study on the efficacy of IPTci.Dimitris Kiosses, Ph.D., an associate professor in clinical psychiatry at Weill Cornell Medical College, discussed Problem Adaption Therapy (PATH), a home-delivered nonpharmacological intervention focusing on emotional regulation. “People with mild cognitive impairment often have behavioral and functional limitations that trigger a lot of negative emotions,” Kiosses told Psychiatric News. These negative emotions include feelings of worthlessness, hopelessness, and helplessness, he added. “Our intervention aims to help them adapt and adjust emotionally to their current situation—such as a recent move in with a family member—by reducing those [negative] emotions and, at the same time, trying to increase positive emotions through engagement in activities that the patients may find pleasurable.”Dimitris Kiosses, Ph.D., says that simple reminders via notes and calendars can help older people with cognitive impairment reduce their symptoms of depression.Vabren WattsPATH focuses on the patient’s ecosystem, which includes the patient, caregiver, and home environment, to address the needs of depressed, cognitively impaired, and disabled elderly adults. Kiosses and colleagues tested the intervention by randomly assigning PATH or supportive therapy (ST-CI) to 74 patients aged 65 and older with major depressive disorder and cognitive impairment for 12 weeks. The results, published January 1 in JAMA Psychiatry, showed that the PATH cohort had a significantly greater reduction in depression than the ST-CI group. In addition, participants receiving PATH were also three times more likely to acheive remission of depressive symptoms after the study’s endpoint than their counterparts who received ST-CI.Kiosses and his research team are now testing PATH in elderly depressed patients who have reported suicidal thoughts. They are also looking into adapting PATH for older adults with cognitive impairment and depression in addition to other comorbid psychiatric illnesses. “Rates for adults with cognitive impairment with and without depression are increasing,” said Kiosses. “With the PATH approach, we are trying to come up with one of the best interventions to reduce depression and increase executive function in our patients.” ■An abstract of “Problem Adaptation Therapy for Older Adults With Major Depression and Cognitive Impairment” can be accessed here. ISSUES NewArchived

Relationship between Antidepressant Prescription Rates and Features of Schizophrenic Patients and Its Outcome in Schizophrenia Treatment

Comorbid depression in schizophrenia is associated with poor outcome, increased risk of relapse and a high rate of suicide. Identification of depressive symptoms and their appropriate treatment is crucial for depressed schizophrenic patients. The aim of this study is to investigate the rates of antidepressant prescription and their outcomes. The records of the schizophrenic outpatients, who were consulted at Psychosis Unit of Psychiatry Department between January 2007 and September 2012, were evaluated retrospectively. Enrolled schizophrenic patients' antidepressant medications were at their minimal effective doses and effective duration. The present study demonstrates that 39 of the 101 patients during their follow-ups were prescribed antidepressants. The mean follow-up period was 6.3 (±4.2) years; the mean age at onset was 22 (±6.5) years; the mean duration of illness was 14.7 (±7.3) years and the mean number of psychotic exacerbation was 5 (±3.7). The most prescribed antidepressants were; sertraline (36.9%), venlefaxine (23.8%) and essitalopram (20.2%). SSRI's were prescribed 57 (73.1%), where as SNRI's 21 times (26.9%). There was no significant difference between SSRI (78.6%) and SNRI (21.4%) treatments in terms of psychotic exacerbation under antidepressant medication. Full remission of depressive symptoms was achieved in 21 patients (53.8%). Remission rates were significantly higher (p<0.01) in SNRI treated depressed schizophrenic patients (85.7%) compared to SSRI treated patients (50.9%). In 8 of the 39 patients (20.5%) antidepressant treatment was terminated due to side effects. This study demonstrates that SSRI's were more often prescribed compared to other classes of antidepressants in emerging depressive symptoms in schizophrenic patients despite full remission with SNRI's is more common. There was no significant difference between SSRI and SNRI treatment in terms of psychotic exacerbation.